Page 717 - Basic _ Clinical Pharmacology ( PDFDrive )

39
R
E
T
H
C
A
P
Adrenocorticosteroids

& Adrenocortical

Antagonists

George P. Chrousos, MD

C ASE STUD Y

A 19-year-old man complains of anorexia, fatigue, dizziness, 1–24 stimulation test, which reveals an insufficient plasma
and weight loss of 8 months’ duration. The examining cortisol response compatible with primary adrenal insuf-
physician discovers postural hypotension and moderate ficiency. The diagnosis of autoimmune Addison’s disease is
vitiligo (depigmented areas of skin) and obtains routine blood made, and the patient must start replacement of the hormones
tests. She finds hyponatremia, hyperkalemia, and acidosis and he cannot produce himself. How should this patient be
suspects Addison’s disease. She performs a standard ACTH treated? What precautions should he take?

The natural adrenocortical hormones are steroid molecules ■ ADRENOCORTICOSTEROIDS
produced and released by the adrenal cortex. Deficiency of
the adrenocortical hormones results in the signs and symp- The adrenal cortex releases a large number of steroids into the
toms of Addison’s disease. Excess production causes Cushing’s circulation. Some have minimal biologic activity and func-
syndrome. Both natural and synthetic corticosteroids are used for tion primarily as precursors, and there are some for which no
the diagnosis and treatment of disorders of adrenal function. They function has been established. The hormonal steroids may be
are also used—more often and in much larger doses—for treat- classified as those having important effects on intermediary
ment of a variety of inflammatory and immunologic disorders. metabolism and immune function (glucocorticoids), those
Secretion of adrenocortical steroids, especially the glucocor- having principally salt-retaining activity (mineralocorticoids),
ticoids, is controlled by the pituitary release of corticotropin and those having androgenic or estrogenic activity (see
(ACTH) (see Chapter 37). Corticotropin is derived from a larger Chapter 40). In humans, the major glucocorticoid is cortisol
protein synthesized in the pituitary, pro-opiomelanocortin and the most important mineralocorticoid is aldosterone.
(POMC). Secretion of the salt-retaining hormone aldosterone Quantitatively, dehydroepiandrosterone (DHEA) in its sulfated
is primarily under the influence of circulating angiotensin and form (DHEAS) is the major adrenal androgen. However,
potassium. Corticotropin has some actions that do not depend on DHEA and two other adrenal androgens, androstenedione
its effect on adrenocortical secretion. However, its pharmacologic and androstenediol, are weak androgens and androstenediol is
value as an anti-inflammatory agent and its use in testing adre- a potent estrogen. Androstenedione can be converted to tes-
nal function depend on its secretory action. Its pharmacology is tosterone and estradiol in extra-adrenal tissues (Figure 39–1).
reviewed only briefly here. Adrenal androgens constitute the major endogenous precursors
Inhibitors of the synthesis or antagonists of the action of the of estrogen in women after menopause and in younger patients
adrenocortical steroids are important in the treatment of several in whom ovarian function is deficient or absent.
conditions. These agents are described at the end of this chapter.

703